DESCRIPTION (Applicant's abstract): Persons with diabetes mellitus suffer delayed or compromised wound repair. Lack of innervation is a major impediment to wound healing and the mechanism by which the nerves mediate their effects remains poorly understood. For example epithelial lesions in the cornea occur in one half of asymptomatic patients and are highly correlated with generalized polyneuropathy. It is hypothesized that factors or peptides are released with injury and that these are altered in diabetic tissue resulting in changes in intercellular communication. The overall goal of this proposal is to determine how injury and the subsequent release of growth factors alters the cellular environment and induces signal transduction mediated events that regulate repair in cells cultured under hyperglycemic conditions or in diabetic tissue. We have developed several wound models using primary and established epithelial and neuronal cells that will be applied to determine how altering the microenvironment or metabolic state affects the wound response. Our overall hypothesis is that the initial injury response can be used to predict the final outcome of the wound response. This would include alterations in signal transduction pathways, the phosphorylation of adhesion proteins and the binding of growth factors.